Glutamate carboxypeptidase 2 (Prostate-specific membrane antigen) (PSMA)

Glutamate carboxypeptidase 2, commonly known as Prostate-Specific Membrane Antigen (PSMA), is a type II transmembrane glycoprotein that is significantly overexpressed in the majority of prostate cancer cases, particularly in advanced and metastatic stages (UniProt P13686). It functions as a zinc-dependent metalloenzyme that catalyzes the hydrolysis of N-acetylaspartylglutamate (NAAG) and folate polyglutamates, though its primary clinical utility lies in its role as a highly specific cell-surface marker (PubMed 35105653). PSMA is a premier target for radioligand therapy and molecular imaging because it internalizes upon ligand binding, enabling the concentrated delivery of therapeutic isotopes like Lutetium-177 (Pluvicto) or imaging agents directly into the cell (FDA 2022). While it is a highly effective target for prostate cancer, its expression in non-prostatic tissues like the salivary glands and kidneys can lead to side effects such as xerostomia (PubMed 34050018). The term "ACPP" in this context likely refers to Prostatic Acid Phosphatase (a distinct prostate marker) or Activatable Cell-Penetrating Peptides, which are experimental technologies designed to improve the delivery of PSMA-targeted agents (PubMed 23719144). Beyond prostate cancer, PSMA is also expressed in the neovasculature of various other solid tumors, suggesting potential applications in a broader range of oncological conditions (PubMed 12444030).

Other names

FOLH1Folate hydrolase 1GCPIIN-acetylated-alpha-linked acidic dipeptidase INAALADase IProstate-specific membrane antigen

Targeted delivery of radionuclides or cytotoxic payloads via binding to the extracellular domain of PSMA and subsequent receptor-mediated internalization.